Fucosyltransferase 3

Fucosyltransferase 3

Fucosyltransferase 3 (FUT3) is an enzyme that plays a crucial role in the biosynthesis of fucosylated oligosaccharides. It is a member of the glycosyltransferase family, specifically involved in the transfer of fucose, a hexose deoxy sugar, to various substrates. FUT3 is encoded by the FUT3 gene in humans and is primarily responsible for the synthesis of Lewis antigens, which are important in cell-cell recognition and adhesion processes.

Structure

Fucosyltransferase 3 is a type II transmembrane protein, which means it has a short N-terminal cytoplasmic tail, a single transmembrane domain, and a large C-terminal catalytic domain located in the Golgi lumen. The enzyme's active site is responsible for the transfer of fucose from the donor substrate, GDP-fucose, to acceptor molecules such as N-acetylglucosamine or galactose residues on glycoproteins and glycolipids.

Function

FUT3 catalyzes the addition of fucose in an α(1,3) linkage to N-acetylglucosamine residues, forming Lewis antigens such as Lewis a (Le^a) and Lewis b (Le^b). These antigens are important in various biological processes, including:

• **Cell adhesion**: Lewis antigens are involved in the adhesion of leukocytes to endothelial cells, a critical step in the immune response.
• **Blood group antigens**: FUT3 is responsible for the synthesis of Lewis blood group antigens, which are important in transfusion medicine.
• **Cancer metastasis**: Altered expression of Lewis antigens has been associated with cancer progression and metastasis.

Clinical Significance

Mutations in the FUT3 gene can lead to the Lewis-negative phenotype, where individuals lack Lewis antigens on their red blood cells and other tissues. This can have implications in blood transfusion and organ transplantation, as well as in susceptibility to certain infections and diseases.

FUT3 expression is also altered in various cancers, and its activity is often upregulated in tumors, contributing to increased metastatic potential. As such, FUT3 is a potential target for cancer therapy, and inhibitors of FUT3 are being investigated for their therapeutic potential.

Genetic Variability

The FUT3 gene is highly polymorphic, with several known alleles that result in different levels of enzyme activity. These genetic variations contribute to the diversity of Lewis antigen expression in the population. The most common alleles include:

• FUT3*01: The wild-type allele with normal enzyme activity.
• FUT3*02: An allele associated with reduced enzyme activity, leading to the Lewis-negative phenotype.

Research and Applications

Research on FUT3 has focused on its role in disease, particularly in cancer and infectious diseases. Understanding the regulation of FUT3 and its interaction with other glycosyltransferases is crucial for developing therapeutic strategies targeting glycosylation pathways.

See Also

• Glycosylation
• Lewis antigen
• Glycosyltransferase